Congestive heart failure (CHF) is a growing epidemic in the Western World, afflicting 5.5 million people in US, with an additional 550,000 new victims diagnosed each year. Even with improved medical devices, acute coronary interventions, and surgical techniques, the one and five year mortality rates for CHF are 10% and 80%, virtually unchanged in the past two decades. The only definitive therapy is heart transplantation, but that remains limited by number (2,200 donor heart available each year) and cost. Ventricular assist devices (VADs), which work in parallel with a failing ventricular by pumping blood, offer an alternative treatment for end-stage heart failure. Previous generation VADs were plagued with complications and durability concerns. A new generation of continuous flow VADs (CFVADs), which utilize a single rotor to impart blood flow are overcoming the limitations of older VADs, significantly reducing complications and achieving one year survival rates approaching that of heart transplants; however, significant challenges remain. Up to 30% of CFVAD recipients experience non-surgical bleeding related to an acquired von Willebrand Factor (VWF) deficiency, thought to be caused by the high shear rates blood experiences as it traverses through the CFVAD. A separate platelet adhesion defect also appears to occur in concert with the VWF alternations. In preliminary studies, we have observed preservation of VWF in VAD recipients with a new CFVAD undergoing clinical trials and in a single patient with a different type of CFVAD whose pump speed was substantially reduced during weaning due to spontaneous cardiac recovery post-VAD implant. Thus, the acquired VWF deficiency does not appear to be inherent to CFVADs and may be altered with changes in design or operation. Given the tremendous need to development treatments for CHF and the potential to reduce a significant complication of CFVAD, we propose to 1) Use a novel microchannel approach to investigate VWF and platelet functional alternations in CFVAD recipients and 2) Using modified microchannels and mock circulatory loops with integral CFVADs, investigate and quantify the shear conditions which produce the observed VWF and platelet dysfunction. PUBLIC HEALTH RELEVANCE: Ventricular assist devices offer the promise to revolutionize the treatment of advanced heart failure. However, complications including bleeding of the stomach and intestines occurs in about 30% of recipients of these devices. In this proposal we seek to understand the causes of this bleeding and ways to reduce or possibly eliminate this risk.